title: Endoplasmic reticulum aminopeptidase associated with antigen processing regulates quality of processed peptides presented by MHC class I molecules.
abstract: Effective immune surveillance by CD8 T cells depends on the presentation of diverse peptides by MHC class I (pMHC I) molecules on the cell surface. The pMHC I repertoire is shaped in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with Ag processing (ERAAP). The ERAAP activity is required for producing peptides of appropriate length for generating optimal pMHC I. Paradoxically, ERAAP also inhibits generation of certain peptides such as the SVL9 (SSVVGVWYL) peptide encoded by the H13(a) histocompatibility gene and presented by D(b) MHC by an unknown mechanism. In this study, we show that the presentation of the SVL9-D(b) complex is inhibited when other peptides compete for binding D(b). Conversely, improving the binding of SVL9 peptide to D(b) suppresses the inhibition. Interestingly, the inhibitory effect of competitor peptides is observed only when ERAAP is expressed in the same cells. Thus, ERAAP, in concert with MHC I molecules, regulates the quality of processed peptides presented on the cell surface.
authors.affiliation: Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
mesh_terms: D000626:Aminopeptidases / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D019556:COS Cells; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D051379:Mice; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology
chemical_list: D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; C110366:OVA-8; D009842:Oligopeptides; D010446:Peptide Fragments; D010047:Ovalbumin; D000626:Aminopeptidases